Cells in living organisms are constantly experiencing a variety of mechanical cues. From the stiffness of the extra cellular matrix to its topography, not to mention the presence of shear stress and tension, the physical characteristics of the microenvironment shape the cells’ fate. A rapidly growing body of work shows that cellular responses to these stimuli constitute regulatory mechanisms in many fundamental biological functions. Substrate strains were previously shown to be sensed by cells and activate diverse biochemical signaling pathways, leading to major remodeling and reorganization of cellular structures. The majority of studies had focused on the stretching avoidance response in near-uniform strain fields. Prior to this work, the cellular responses to complex planar strain fields were largely unknown. In this thesis, we uncover various aspects of strain sensing and response by first developing a tailored lab-on-a-chip platform that mimics the non-uniformity and complexity of physiological strains. These microfluidic cell stretchers allow independent biaxial control, generate cyclic stretching profiles with biologically relevant strain and strain gradient amplitudes, and enable high resolution imaging of on-chip cell cultures. Using these microdevices, we reveal that strain gradients are potent mechanical cues by uncovering the phenomenon of cell gradient avoidance. This work establishes that the cellular mechanosensing machinery can sense and localize changes in strain amplitude, which orchestrate a coordinated cellular response. Subsequently, we investigate the effect of multiple changes in stretching directions to further explore mechanosensing subtleties. The evolution of the cellular response shed light on the interplay of the strain avoidance and the newly demonstrated strain gradient avoidance, which were found to occur on two different time scales. Finally, we extend our work to study the influence of cyclic strains on the early stages of cancer development in epithelial tissues (using MDCK-RasV12 system), which was previously largely unexplored. This work reveals that external mechanical forces impede the healthy cells’ ability to eliminate newly transformed cells and greatly promote invasive protrusions, as a result of their different mechanoresponsiveness. Overall, not only does our work reveal new insights regarding the long-range organization in population of cells, but it may also contribute to paving the way towards new approaches in cancer prevention treatments.

Dissertação(mestrado) - Universidade Federal do Rio Grande, Programa de Pós-Graduação em Educação Ambiental, Instituto de Educação, 2005. / Submitted by eloisa silva (eloisa1_silva@yahoo.com.br) on 2012-09-17T19:59:17Z No. of bitstreams: 1 dissertacao sn.pdf: 1183476 bytes, checksum: 0afcb61bd00e964668a4ed9f7f2170c4 (MD5) / Approved for entry into archive by Bruna Vieira(bruninha_vieira@ibest.com.br) on 2012-12-02T12:57:35Z (GMT) No. of bitstreams: 1 dissertacao sn.pdf: 1183476 bytes, checksum: 0afcb61bd00e964668a4ed9f7f2170c4 (MD5) / Made available in DSpace on 2012-12-02T12:57:35Z (GMT). No. of bitstreams: 1 dissertacao sn.pdf: 1183476 bytes, checksum: 0afcb61bd00e964668a4ed9f7f2170c4 (MD5) Previous issue date: 2005 / O presente estudo de caso tem como objetivo compreender os significados e os sentidos atribuidos por um grupo de trabalhadores e trabalhadoras às suas relações interpessoais e socioambientais a partir de uma experiência educacional promovida pelo Sindicato da Alimentação, por meio do Projeto Integrar, que certificou o ensino fundamental. A proposta é analisar as implicações e repercussões dessa experiência em suas vidas, envolvendo superações e permanências. O princípio orientador dessa construção é a dimensão ontológica do trabalho na constituição do ser humano, tendo a abordagem sócio-histórica – que compreende o sujeito através de sua atividade social e histórica e que se constitui a partir das relações sociais – como pano de fundo para a apreensão dos sujeitos pesquisados. O aporte teórico utilizado para construir e analisar os aspectos educacionais – ambiental e não formal – ancorou-se na pedagogia transformadora, a pedagogia do oprimido rumo a sua libertação. A abordagem qualitativa apoiou-se nos pressupostos dialéticos; a construção teórico- metodológica, os procedimentos utilizados para organizar, analisar e interpretar os dados das entrevistas semi-estruturadas, foram sustentados na orientação de Freire, a partir do Tema Gerador como categoria de análise e dos subtemas que dele emergiram, e se pautou na análise de conteúdo. Os dados analisados revelaram que para os pesquisados a experiência significou a superação da visão ingênua do mundo vivido, através da consciência crítica construída nas experiências cotidianas, na inserção comunitária como integrantes de sua classe e nas mediações inter e intrapsicológicas. As decisões coletivas que assumiram pautaram-se muito além das necessidades materiais, foram construídas como uma dimensão afirmativa da cidadania, da dignidade humana e da capacidade de dirigir seus destinos com autonomia, tendo, nesse caso, o fator subjetivo como campo de luta na superação das condições socioambientais adversas. Para que essa suposta transformação não se reduza a momentos, mostra-se necessário sua organização permanente enquanto classe trabalhadora, discutindo e avaliando constantemente os movimentos e transformações do real e, nesse sentido, redirecionando sua ação transformadora. / This study of case paper aims to comprehend the means given for a male and female works group in their relationships and socio-environmental through the educational experience promoted by Feeding Union, through Integrar Project that certificated the primary school. The purpose is analyse the implications and repercussions from this experience in their lives and improve their critic consciousness. The concept of this construction is a real dimension of the work in human’s constitution, it has socio-historic approach – that comprehend the subject through it social and historic activities constituted in relationships – like a background that will apprehend searches subjects. The theoretical to build and analyse educational aspects – non-formal and environmental – was transformer educational, the pedagogy of the oppressed toward their freedom. The qualitative approach was in dialectical knowledge; theoretical-methodology build, the procedures to organise, analyse and interpret interviews semi-organized, before interpreted by Freire, using Tema Gerador and it other themes. The analysis showed that the experiences had surpassed naive vision of the world through a critic consciousness everyday, in their same socio-economic class community and relations inter and intra-psychologic to the searches. They had their decisions besides of the material need, but like a citizenship assertion, human dignity and capacity to guide their destinies with autonomy, the subjectivity is a battlefield to overcome contrary socio-environmental conditions. To this supposed transformation really work, be necessary it constantly organisation while work class, discussing and assessing all movements and transformations from real to the transformer actions.

O choque hipovolêmico foi induzido em 14 ratos machos através de sucessivos sangramentos de 3,1 ml de sangue para cada 100 g de peso. Após o período de sangrias, foi iniciado o tratamento com solução salina isotônica (7,5 % NaCl por 0,4 ml/g de peso) ou hipertônica (0,9 % NaCl por 0,4 ml/g de peso). Iniciando com o sinal basal, a aquisição de dados da pressão arterial foi feita durante todo o experimento que durou aproximadamente 30 minutos. O objetivo deste trabalho é analisar a variabilidade do débito cardíaco durante a indução do choque e identificar se o mecanismo de compensação de perda de volume está funcionando. A análise está focada no débito cardíaco porque ele depende linearmente do volume sistólico e da freqüência cardíaca. Um método não invasivo foi implementado para calcular o volume sistólico diretamente do sinal da pressão arterial. A análise wavelet foi usada para encontrar as freqüências principais do sinal da pressão arterial e também suas variabilidades durante cada estágio. Durante o experimento, a estabilidade do débito cardíaco era esperada, pois a freqüência cardíaca deve aumentar para compensar a perda de volume. Na maioria dos casos foi observado que a freqüência aumenta nos dois primeiros estágios, seguida de uma queda significativa. Como conseqüência o débito cardíaco diminuiu durante os estágios intermediários, mostrando que o mecanismo de compensação não estava funcionando apropriadamente. Em três casos, as freqüências aumentaram somente no estágio final. Esta anomalia sugere uma investigação mais profunda incluindo resposta ao tratamento e acompanhamento da evolução do choque / Hypovolemic shock was induced in fourteen male rats by successive bleeding. During 30 minutes, after base signal acquisition, 3.1ml of blood for each 100g of weight was collected. After this period, a treatment was initiated with isotonic saline solution (7.5 % NaCl each 0.4 ml/g of weight) or hypertonic (0.9 % NaCl each 0.4 ml/g of weight). The arterial pressure signal was captured during all the experiment. The goal of this work is to analise the variability of the cardiac debit during the induction of shock and identify whether the physiological mechanism to compensate the loss of volume is working. The analysis is focused on the cardiac debit because it depends linearly on systolic volume and cardiac frequency. A non-invasive method was implemented to calculate the systolic volume directly from the arterial pressure signal. Wavelet analysis was used to find the main frequencies and also their variability during each stage. The cardiac debit stability was expected, during experiment because the cardiac frequency must increase to compensate the lost of volume. In most cases was observed that the frequency increases in the first two stages followed by a significant decrease. As a consequence the cardiac debit decreases during the intermediate stages, showing that the compensation mechanism was not working properly. In three cases the frequencies increased only in the final stage. This anomalie suggests a deeper investigation including response to treatment and shock evolution

The transformed rejection method, a combination of inversion and rejection, which can be applied to various continuous distributions, is well suited to generate binomial random variates as well. The resulting algorithms are simple and fast, and need only a short set-up. Among the many possible variants two algorithms are described and tested: BTRS a short but nevertheless fast rejection algorithm and BTRD which is more complicated as the idea of decomposition is utilized. For BTRD the average number of uniforms required to return one binomial deviate lies between 2.5 and 1.4 which is considerably lower than for any of the known uniformly fast algorithms. Timings for a C-implementation show that for the case that the parameters of the binomial distribution vary from call to call BTRD is faster than the current state of the art algorithms. Depending on the computer, the speed of the uniform generator used and the binomial parameters the savings are between 5 and 40 percent. (author's abstract) / Series: Preprint Series / Department of Applied Statistics and Data Processing

The aim of this study is to explore some of the ways in which masculinity is constructed in relation to HIV/AIDS. A review of literature about masculinity describes a normative masculinity where being a man is often associated with harmful practices. The review also shows that such a normative conceptualisation of masculinity has been contested through a call for less rigid and simplistic descriptions of what it means to be a man. The literature review also shows that research that specifically addresses the intersection between masculinity and HIV/AIDS tends to provide a marginalising and negative account of men’s position in the epidemic. However, it also shows a growing awareness of the inadequacy of such an approach. The present study aims to critically explore the ways in which masculinity is constructed by a group of men living with HIV. More specifically it explores how men living with HIV experience their masculinity and whether their HIV status impacts on their views of themselves as men. The study is located in a social constructionist framework and utilises a qualitative methodological approach. Discourse analysis was used to analyse the text produced during focus group discussions with a group of black South African men who are living with HIV. From the discourse analysis, six discourses were identified as operating in the text. The first three discourses can be described as contributing to an idealised or normative construction of masculinity. This idealised masculinity is constructed by the participants as something that is valued and to which men need to conform. At the same time it is also constructed by the participants as something that men cannot always attain and that they experience as a burden in that they continually need to engage in actions that affirm their position as ‘real’ men. This tension is constructed as a sense of not being able to ‘live up to’ hegemonic notions of masculinity that participants describe as being valued by their partners, family members and others in their community. </p > This construction of masculinity was spoken of as operating in a restrictive manner, where men are limited in the kind of actions available to them, such as seeking support or acknowledging their vulnerability to HIV. Specific discursive acts were mentioned as contributing to this idealised masculinity, such as getting married, having children, being a financial provider, having multiple sexual partners and being in a position of authority in the home. In the last three discourses that were identified the manner in which HIV contributes to constructions of masculinity became a more prominent feature of the discourses. Participants constructed HIV as a life event that interferes with conforming to notions of a normative masculinity. This emerged in talk of how illness or other periods of vulnerability disrupts the notion of men being invulnerable. It also emerged in talk of how living with HIV complicates attaining traditional signifiers of masculinity, such as getting married or having children. The final discourse that emerged from the text relates to a transformed masculinity, where men living with HIV reconstruct their masculinity in the face of the challenges that HIV poses. Living with HIV is constructed as requiring of men to re-evaluate and change their masculinity as conforming to normative constructions of masculinity is perceived as restrictive and harmful. Such an idealised masculinity prevents men from accessing the support they need in managing their health and men therefore look towards change. The study contributes to the growing body of research that explores masculinity as fluid and constructed in relation to various influences, rather than viewing masculinity as a fixed identity. It presents an account of how men living with HIV challenge and resist dominant constructions of masculinity, thereby indicating that there are possibilities for change. This has implications for interventions that aim to increase the potential positions men can assume in promoting responsible sexual practice as well as deconstructing notions of masculinity that limit the courses of action available to men living with HIV when seeking support. / Dissertation (MA)--University of Pretoria, 2008. / Psychology / unrestricted

Contrast is an important factor in any subjective evaluation of image quality. It is the difference in visual properties that makes an object distinguishable from other objects and background. Contrast Enhancement method is mainly used to enhance the contrast in the image by using its Histogram. Histogram is a distribution of numerical data in an image using graphical representation. Histogram Equalization is widely used in image processing to adjust the contrast in the image using histograms. Whereas Gamma Correction is often used to adjust luminance in an image. By combining Histogram Equalization and Gamma Correction we proposed a hybrid method, that is used to modify the histograms and enhance contrast of an image in a digital method. Our proposed method deals with the variants of histogram equalization and transformed based gamma correction. Our method is an automatically transformation technique that improves the contrast of dimmed images via the gamma correction and probability distribution of luminance pixels. The proposed method is converted into an android application. We succeeded in enhancing the contrast of an image by using our method and we have tested for different alpha values. Graphs of the gamma for different alpha values are plotted.

The acceptance-rejection algorithm is often used to sample from non-standard distributions. For this algorithm to be efficient, however, the user has to create a hat function that majorizes and closely matches the density of the distribution to be sampled from. There are many methods for automatically creating such hat functions, but these methods require that the user transforms the density so that she knows the exact location of the transformed density's inflection points. In this paper, we propose an acceptancerejection algorithm which obviates this need and can thus be used to sample from a larger class of distributions. / Series: Research Report Series / Department of Statistics and Mathematics

Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / High dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) who are chemosensitive to salvage therapy. There is now evidence that the achievement of complete remission by PET scan (PET-CR) after salvage therapy is a favorable determinant of ASCT outcome, implying that PET response should be part of the prognostic assessment for patients considering ASCT. However, it is unclear whether other prognostic factors are still relevant in patients getting post-salvage PET scanning. Moreover, while ASCT is often also used for patients with R/R transformed indolent lymphoma (TIL), there are no data on whether prognostic factors that are important for DLBCL patients, especially PET response to salvage, are similarly prognostic in this population. We conducted a retrospective study of 143 patients with R/R DLBCL and TIL who were transplanted in the last decade and had a post-salvage PET scan prior to ASCT. We examined prognostic factors in both groups, and constructed a prognostic score for DLBCL patients. For patients with DLBCL, post-salvage PET response was an important prognostic factor. Advanced age and symptomatic relapse were also significantly associated with inferior outcome. A simple score could stratify patients into 3 risk groups with 4-year post-ASCT overall survival of 84%, 59%, and 10%, and 4-year progression-free survival of 67%, 41% and 0% (p<0.0001 for both). However, none of those factors (including PET response to salvage) could be demonstrated for TIL, likely because of the limited sample size. Our novel prognostic score for DLBCL patients undergoing ASCT may be useful for prognostication, for stratification in clinical trials, and to motivate the design of new strategies for patients in the highrisk group, who may not derive benefit from standard ASCT. Those factors, however, do not apply to patients with TIL, which has important implications for their treatment and inclusion in ASCT clinical trials with larger sample sizes. / 2031-01-01

Untersuchungen zu standortunabhängigen Eigenschaften des Wachstums für verschiedene Baumarten unter Verwendung einer Polynommethode und mit Hilfe des Evolonmodells.

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation in the nucleus, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, pretreatment with an autophagy inhibitor offsets the effects of MG132 on CHK1 and RAD51 levels. These findings imply that p62 accumulation in the nucleus in response to autophagy inhibition promotes proteasome-mediated CHK1 and RAD51 protein instability. This claim is further supported by the findings that transient expression of a p62 mutant, which is constitutively localized in the nucleus, in B cell lines with low endogenous p62 levels recaptures the effects of autophagy inhibition on CHK1 and RAD51 protein stability. These results indicate that proteasomal degradation of RAD51 and CHK1 is dependent on p62 accumulation in the nucleus. However, small hairpin RNA (shRNA)-mediated p62 depletion in EBV-transformed lymphoblastic cell lines (LCLs) had no apparent effects on the protein levels of CHK1 and RAD51, likely due to the constitutive localization of p62 in the cytoplasm and incomplete knockdown is insufficient to manifest its nuclear effects on these proteins. Rather, shRNA-mediated p62 depletion in EBV-transformed LCLs results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination, indicative of activation of RNF168-mediated DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis.